1. Field of the Invention
The present invention relates to the use of antioxidants to reduce the effects of radiation on humans.
2. Description of Related Art
Ionizing radiation (X-rays and gamma rays) has proven to be a double-edged sword in clinical medicine since its discovery by Dr. Wilhelm Roentgen in 1895 (1, 2). Energy wavelength progresses along the electromagnetic continuum from longer ranges (radiowaves, microwaves, infrared, heat waves) to medium wavelengths (visible light, ultraviolet light) to shorter wavelengths (ionizing radiation, e.g., x-rays and gamma rays). It is these x-rays and gamma rays that are able to drive electrons out of their normal atomic orbits with enough kinetic energy to generate charged molecules (including free radicals) that damage cells. In addition to the initial realization by the medical community that ionizing radiation could detect as well as treat human diseases, came the unfortunate demonstration that it could also induce serious illness.
In fact, most of the ionizing radiation to which the human population is exposed, other than that received from environmental sources, is from the diagnostic and screening imaging machines employed by today's clinical healthcare professionals. For example, in the past, x-ray-induced skin cancers were noted with higher frequency in radiologists. Obviously, whenever x-rays are employed, it is done with caution so that patients and healthcare providers are exposed to as low a dose as possible. Physicists and nuclear engineers have devised improved equipment and radiation beam delivery systems to reduce the level of diagnostic radiation dose without compromising the quality of images. However, radiation biologists agree that there is no threshold dose below which there is no risk of cellular damage. In fact, even a single radiation track that crosses a cellular nucleus has a very low, but finite, probability of generating damage that may result in cellular dysfunction, structural mutations, and subsequent genetic implications.
While most clinical radiologists believe the risks of x-ray exposure are very small, residual biologic effects from alteration in structure are dependent on whether the cell repairs its injured components. Although the vast majority of damage is repaired, some may be unrepaired or misrepaired and therein lies the problem. In adults, most radiation researchers consider cancer induction to be the most important somatic effect of low dose ionizing radiation and this outcome may occur in nearly all the tissues of the human body. Academic radiologists are also raising future disease concerns regarding pediatric age groups because of the increased numbers of imaging studies now being performed in younger populations (3). In light of these concepts, the healthcare profession states that ionizing radiation exposure should only occur when there is a defined healthcare benefit, or indicated when the risk-benefit ratio is favorable to the patient. The critical concept has been always to protect humans by physical local factors, such as shielding and decreasing doses and x-ray times. However, no one has previously considered the additional aspects related to a strategy of systemic biological protection.
Recent advances in imaging technology have made possible the detection of many illnesses such as heart disease, cancer, neurologic diseases, arthritis and other acute or chronic conditions. It is also a significant development that this technology may detect the problem at an early stage when treatment interventions allow for less invasive therapeutic procedures and/or surgical operations and yet achieve improved health outcomes. In this environment, the number of diagnostic x-rays performed is truly enormous. It was estimated in the United States for the period 1985 to 1990 at least 800 diagnostic studies per 1,000 population were performed and this excluded dental x-rays and nuclear medicine (4). The importance of these findings can be appreciated since it is probable that frequent low dose radiation exposures may be more damaging than a single higher dose exposure on the criteria of gene mutations and cancer promotion.
The current era has seen an explosion of diagnostic imaging equipment including the introduction of computed tomography, digital radiography, expanded nuclear medicine applications, interventional radiology, and lengthening fluoroscopic procedures. In concert with these technical innovations, the concept of early disease detection and screening large populations to employ illness prevention strategies will generate further rapid expansion of members of imaging studies with increased ionizing radiation exposure to the public. As a direct consequence of this new proactive healthcare approach, imaging will be performed in many more, otherwise healthy, people and asymptomatic “at risk” populations. In addition, initial exposures will occur at an earlier age and the mandate of serial follow-up imaging will result in an overall greater frequency of x-ray studies.
The doses of ionizing radiation exposure in imaging studies vary dramatically from less than 0.1 rem (1 millisievert, mSv, for x-rays and gamma rays, 1 rem=1 rad) per test for some procedures to others that involve levels in some organs in excess of 25 rem per test. Table 1 lists a sampling of common studies (5-8). Note that while the red marrow dose is usually the reported “standard,” the actual target organ dose is actually often significantly higher. For example, mammography exposes the actual breast tissue to approximately 700 mrem, virtually equal to the total skin entrance dose. Likewise, thallium scanning exposes the thorax to approximately 1000 mrem, about 20 times the red marrow dose.
TABLE 1SkinEffective DoseEntranceProcedureEquivalent (HE)DoseDiagnostic X-raymSv*mremmremChest AP, 100 kVp0.0151.510Lumbar spine AP,0.27327.335980 kVpUpper G.I.4.1410 2300/minCoronary angioplasty 50–150/ 5000–15000/25000/minminminHead CT0.8–5  80–5004500Abdomen CT6–24600–24002000Dental0.011350Electron beam CT heart0.14–0.3 14–30150Mammogram****700Nuclear MedicinemSvmremmrem18F-Fluorodeoxyglucose,9.99999NA10 mCi99 mTc-MAA Lung scan2.03203NA(perfusion only) 5 mCI99 mTc-HDP Bone scan5.92592NA20 mCi201Tl Thallium scan25.532553NA3 mCi*Seivert is the official international unit of biological radiation dose. One Sv = 100 rem.ND = Data not available** = Dose negligibleNA = Not applicable
Depending on the age of the individual, frequency of testing, exposure time, and total dose, the diagnostic or screening imaging studies could increase the risk of somatic damage (some forms of cancer such as leukemia, breast, and thyroid) as well as genetic damage (such as with gonadal exposure) in the target population. In fact, radiation experts are beginning to call for special attention to issues of exposure from CT Scanning in younger patients (9). It should be emphasized that the risk of radiation injury produced by diagnostic doses below 0.5 rem is very small in comparison to other agents that are present in the diet or the natural environment. However, regardless of the “insignificant” risk with any individual exposure or imaging event, the total effects of ionizing radiation are on-going, cumulative over time, have the potential for lifelong expression, and may have a future generational genetic impact.
It should be anticipated that as more sophisticated imaging studies are available for diagnosis and screening, the individual small risks may add up over a lifetime. For example, nuclear medicine has been expanded to new techniques which include intravenous systemic injection of radionuclides and expose various body organs to differing radiation doses (10). The recent impact of interventional techniques often combined with surgical procedures also increases the imaging risks. Furthermore, advanced fluoroscopic imaging used for technical procedures such as percutaneous transluminal angioplasty, transhepatic cholangiography, stent and drainage placements, as well as venous access procedures may involve significant radiation exposure (11). In fact, by the year 2000 in the United States alone, about 750,000 patients underwent coronary balloon angioplasty (12). Finally, the most recent technical innovations utilized in screening procedures, such as spiral and electron beam computed tomography for heart, lung, colon, and total body scanning are new clinical areas where issues of radiation dosimetry have to be considered (13, 14).
Currently, the FAA and airlines consider flight personnel (including flight attendants) as radiation workers. As such, they are allowed a regulatory dose limit 50 times the dose limit allowable to the general public. According to recent estimates, over 400,000 frequent fliers travel over 75,000 air miles each year, which means that they will exceed radiation dose limits to the general public from galactic (cosmic) radiation during flight (15). The radiation exposure during flight varies with altitude, flight time, air route, and solar flare activity. As an example, a routine flight from New York to Chicago (highest altitude 37,000 feet) yields a radiation dose rate of 0.0039 mSv per block hour. (The block hour begins when the aircraft leaves the blocks before takeoff and ends when it reaches the blocks after landing.) A flight from Athens, Greece, to New York (highest altitude 41,000 feet) yields a radiation dose rate of 0.0063 mSv per block hour. The total radiation dose form the New York to Chicago route is 0.0089 mSv and the Athens to New York flight is 0.0615 mSv. For reference, the annual exposure limit for the general public is 1 mSv. The only remediation recommended by the FAA for radiation exposure during flight is to limit flight and avoid traveling during periods of increased solar flare activity. Airline crew members flying long-haul high-altitude routes receive, on average, greater exposures each year than do radiation workers in ground-based industries where radioactive sources or radiation-producing machines are used (16).
The United States military is aware of and concerned about potential radiation exposures to our troops. Perhaps the most obvious population at risk in the military are pilots flying long, high-altitude missions. The expected radiation doses would be in accordance with the estimates outlined above. The most recent U.S. Army study on the issue recognizes four nuclear radiation exposure risk categories of military personnel based on their likelihood and extent of exposure (17, Table 2). The Army currently has three radiation protection programs to address these risk categories. One is applied to those individuals whose duties parallel those of civilian radiation workers. These include military personnel, such as x-ray technicians, radiologists who do radiological examinations, researchers who use radionuclides, and technicians who maintain radioactive commodities, such as radiation detection instruments and calibration sources. The second applies to soldiers whose primary occupation does not usually expose them to radiation. These are soldiers who might respond to a military situation, such as that covered by Allied Command Europe Directive (ACE) 80-63, in which radiation is present, but at doses not exceeding 700 mSv. The third category applies to those situations involving extremely high radiation exposure, such as nuclear war.
TABLE 2Revised, Low-Level Radiation Guidance forMilitary OperationsRadiationIncreasedTotalExposureRisk ofCumulativeStateRecommendedLong TermDoseaCategoryActionsFatal Cancerb<0.5mGy0NoneNone0.5–5mGy1ARecord individual1:4,000dose readingsInitiate periodicmonitoring5–50mGy1BRecord individual1:400dose readingsContinue monitoringInitiate rad surveyPrioritize tasksEstablish dosecontrol measure aspart of operations50–100mGy1CRecord individual1:200dose readingsContinue monitoringUpdate surveyContinue dose-control measuresExecute prioritytasks onlyc100–250mGy1DRecord individual1:80dose readingsContinue monitoringUpdate surveyContinue dosecontrol measuresExecute criticaltasks onlyd250–700mGy1ERecord individual1:30dose readingsContinue monitoringUpdate surveyContinue dosecontrol measuresExecute criticaltasks onlyd
aThe use of the measurement millisievert is preferred in all cases. However, due to the fact that normally the military has only the capability to measure milligray (mGy), as long as the ability to obtain measurements in millisievert is not possible, U.S. forces will use milligray. For whole body gamma irradiation, 1 mGy is equal to 1 mSv. All doses should be kept as low as reasonably achievable (ALARA). This will reduce the risk to individual soldiers and will retain maximum operational flexibility for future employment of exposed soldiers.
bThis is in addition to the 1:5 and 1:4 incidence of fatal cancer among the general population. Increased risk is given for induction of fatal cancer (losing an average of 24 years of life for personnel ages 20-30 years). It must be noted that higher radiation dose rates produce proportionately more health risks than the same total dose given over a longer period.
cExamples of priority tasks are those missions to avert danger to persons or to prevent damage from spreading.
dExamples of critical tasks are those missions required to save lives.
This study committee made four recommendations:    1) When making decisions, commanders should consider the long-term health effects that any action may have on their troops. This recommendation was extended such that it became standard operating policy.    2) The U.S. Department of Defense should develop and clearly express an underlying philosophy for radiation protection. Specifically, the committee suggested,
a: application and adaptation of the system recommended by the International Commission of Radiological Protection,
b: in peacetime or nonemergency situations, soldiers should be accorded the same level of protection accorded civilians, and
c: in settings in which an intervention is required and specific numerical dose limits are neither applicable nor practical, commanders should justify the mission (there is more benefit than risk), examine competing risks, and optimize the mission (identify ways to minimize dose without jeopardizing the mission).    3) Military personnel should receive appropriate training in both radiation effects and protection. Their training will need to vary on the basis of the particular level of potential exposure and the task at hand.    4) A program of measurement, recording, maintenance, and use of dosimetry and exposure information is essential.
The programs, once again, include no protection measures other than controlling time, distance, and physical shielding.
Radiation workers experience a broad spectrum of working conditions that have radiation exposure as a normal part of the workplace environment. Examples include medical radiology workers, nuclear power plant workers, and workers who use radiation and radioactive materials in research. As mentioned above, commercial flight crews are also considered to be radiation workers. Owing to this occupational classification, radiation workers are allowed to receive 50 times the radiation dose allowed to the general public. Radiation workers also differ from the general public in that they receive training about the risks of radiation exposure and are monitored for their radiation exposure as part of their working paradigm. The nuclear regulatory commission (NRC) has established occupational dose limits as noted previously and procedures for monitoring and record-keeping. These standards and regulations rely solely on time, distance, and physical shielding as methods of radiation protection.